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<center><h2>Introduction</h2></center>
<p>
The <a href="http://clinicaltrials.gov/ct/show/NCT00000526" target="other">
Cardiac Arrhythmia Suppression Trial (CAST)</a> was a landmark NHLBI-sponsored
study designed to test the hypothesis that the suppression of asymptomatic or
mildly symptomatic ventricular premature complexes (PVCs) in survivors of
myocardial infarction (MI) would decrease the number of deaths from ventricular
arrhythmias and improve survival. Enrollment required an acute MI within the
preceding 2 years and 6 or more PVCs per hour during a pre-treatment
(qualifying) long-term ECG (Holter) recording. Those subjects enrolled within
90 days of the index MI were required to have left ventricular ejection
fractions less than or equal to 55%, while those enrolled after this 90 day
window were required to have an ejection fraction less than or equal to
40%. CAST enrolled 3,549 patients in all.
<p> After initial qualification, patients in CAST were randomly assigned to
receive encainide, flecainide, moricizine (antiarrhythmic drugs) or a placebo.
Patients who had significant suppression of PVCs with a particular agent were
then continued on that agent or on placebo. In April of 1989, the Data and
Safety Monitoring Board recommended that the encainide and flecainide arms of
the study be discontinued because of excessive mortality in the drug arms of
the trial primarily due to arrhythmia, acute MI with shock, or chronic
congestive heart failure.
<p>CAST was then followed by CAST-II, which involved continuation of the
moricizine arm of the CAST and placebo. CAST-II was divided into two blinded,
randomized phases: an early, 14-day exposure phase that evaluated the risk of
starting treatment with moricizine after MI and a long-term phase that
evaluated the effect of moricizine on survival after MI in patients whose PVCs
were either adequately suppressed by moricizine or only partially suppressed.
CAST-II was stopped early because long-term treatment with
moricizine after an MI was associated with a trend to excess mortality as
compared with no treatment or placebo.
<p>The CAST-II study authors concluded that as with the other antiarrhythmic
agents used in CAST (flecainide and encainide), the use of moricizine to
suppress asymptomatic or mildly symptomatic ventricular premature complexes
after MI was not only ineffective but also harmful.
<p>In order to investigate further the relationship between survival and changes in
heart rate variability in response to anti-arrhythmic treatment, Phyllis
K. Stein, Ph.D., of Washington University, St. Louis, obtained pre-treatment
(qualifying) and on-therapy (suppression) long-term ECG recordings from
participants in CAST (including CAST II) from the CAST data coordinating
center. She selected for study a subset of the CAST patients, consisting of
those who
<ul>
<li> had usable pre-treatment and on-therapy recordings, based on data
collected during the original CAST and CAST II studies</li>
<li> received a randomly-assigned antiarrhythmic treatment that successfully
reduced their PVC rates by at least 80% on the first attempt, and</li>
<li>continued on that treatment.</li>
</ul>
<p>These criteria were satisfied by 734 patients, of whom 69 died during the
study period. The CAST RR Interval Sub-Study Database consists of RR interval
time series from the pre-treatment and on-therapy recordings from these
patients. The database also includes data from 75 additional subjects for
whom only one acceptable recording was available but who satisfied the other
selection criteria. A small number of subjects included in this database
were excluded from Dr. Stein's study because of the occurrence of atrial
fibrillation or paced rhythm.
<p>All recordings were scanned by an experienced research arrhythmia analyst,
using standard Holter analysis procedures. Beat annotation files were edited in
a second pass to identify improperly measured RR intervals to be excluded from
further analysis. A limited amount of additional information has been recorded
in a header (.hea) file for each record.
<p>
This database has several important limitations:</p>
<ol>
<li> Sixty percent of the tapes were recorded on reel-to-reel recorders or
other recorders that lacked a calibrated timing signal. Such recordings are
likely to contain frequency-domain artifacts, the result of variations in the
speed of tape recording or playback (wow and flutter), which, if unrecognized,
can confound analysis of heart rate variability. The header (.hea) file for
each record indicates if a calibrated timing signal was recorded.</li>
<li> The purpose of the analysis was to identify N-N intervals
accurately. Manually inserted beats were always labeled as Q (unclassified).
Great effort was made to identify beats with mismeasured onset points;
these beats were also labeled as Q.</li>
<li> Attention was given primarily to N-N intervals of durations that fall
between limits indicated in the .hea file for each record. Little effort was
made to correct N-N intervals with unusually short or long durations; beats
following such intervals were labeled as Q. Therefore, although beats
identified as V or A are almost certainly premature ventricular or
supraventricular beats, respectively, their incidences are probably
underestimated.</li>
<li> The original ECG signals are not available. Accordingly, it is not
possible to verify the recorded intervals, to identify or correct errors
in beat labels or location, or to study features of the ECG other than
inter-beat intervals.
<li> The RR interval time series contain small numbers of anomalously long
intervals that typically result from errors in beat detection during the
standard Holter analysis. For example, if a single beat is missed, an interval
that is about twice as long as the correct intervals appears in the RR interval
time series. These long intervals appear as noise in the RR interval time
series. It is possible that rare sinus pauses may also account for a few of
these long intervals, but this cannot be verified since the original ECG
signals are unavailable.
</ol>
<p>This significant collection of time series, comprising in aggregate about
150 million RR intervals, has been contributed to PhysioNet by Dr. Stein, with
the consent of the NHLBI. Limited access to additional data from the original
CAST and CAST II studies is available to qualified investigators on application
to the NHLBI; see the <a
href="http://www.nhlbi.nih.gov/resources/deca/descriptions/cast.htm"
target="other">CAST page</a> on the NHLBI's web site.
<p>
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